2023, Vol. 27 ›› Issue (2): 258-263

Total flavonoids of Hippophae rhamnoides L. interfere with the regression of hypertrophic scar tissue blocks in a rabbit ear model

Niu Zihan, Yu Yang, Ai Jiang, Bu Panpan, Li Wenbo, Suriye·Reheman, Ma Shaolin   

Abstract: BACKGROUND: Total flavonoids of Hippophae rhamnoides L. can inhibit fibrosis in the kidney, liver and myocardium. However, related studies on hypertrophic scar fibrosis are rarely reported.
OBJECTIVE: To observe the effect of total flavonoids of Hippophae rhamnoides L. on the regression of hypertrophic scar in a rabbit ear model and to explore its mechanism.
METHODS: Eight New Zealand white rabbits were selected for the study. Three round wounds with a diameter of 8 mm were made on both sides of each ear along the ventral midline, a total of 96 wounds. After 21 days of wound epithelization, all rabbits were randomly divided into five groups: 0.5, 1.0, 2.0 g/L total flavonoids of Hippophae rhamnoides L. groups, two rabbits in each group, and dimethyl sulfoxide group (drug solvent control) and blank control group, one rabbit in each group. Corresponding drugs were injected into the base of tissue once every 3 days for 4 continuous weeks. The pathological changes of hypertrophic scar tissue blocks were observed and compared by hematoxylin-eosin staining and Masson staining. The expressions of type I and III collagen mRNAs in rabbit ear scar tissue were detected by real-time PCR. Western blot was used to detect the expression of type I and III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor proteins in rabbit ear scar tissue blocks.
RESULTS AND CONCLUSION: General observation: The scar tissue was softened and flattened significantly after the injection of different concentrations of total flavonoids of Hippophae rhamnoides L. In the blank control group, there were a large number of infiltrated inflammatory cells, angiogenesis and irregular arrangement of collagen fibers. Compared with the blank control group, the neat distribution and loose arrangement of fascicular collagen fibers could be observed in different concentration treatment groups, especially in the 2 g/L group. Scar elevation index and collagen fiber area density in different concentration treatment groups were significantly lower than those in the blank control group and dimethyl sulfoxide group (P < 0.05). The expression levels of type I and III collagen mRNAs in scar tissue were significantly lower in different concentration treatment groups than the blank control group (P < 0.05). The collagen transcription was most significantly downregulated in the 2 g/L treatment group. Compared with the blank control group, dimethyl sulfoxide could partly inhibit the expression of type III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor. However, different concentrations of total flavonoids of Hippophae rhamnoides L. could sufficiently inhibit the expression of type I and III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor in rabbit ear scar tissue in a concentration-dependent manner. To conclude, total flavonoids of Hippophae rhamnoides L. can inhibit scar hyperplasia, soften and flatten the scar tissue and lighten the color of scar tissue, which treat hypertrophic scar by reducing the expressions of transforming growth factor β1, type I and III collagen in rabbit ear scar tissue blocks, inhibiting the transformation of fibroblasts into myofibroblasts and reducing angiogenesis in scar tissue.
Key words: total flavonoids of Hippophae rhamnoides L., hypertrophic scar, collagen fiber, transforming growth factor β1, vascular endothelial growth factor